Tailoring Stress Cardiac MRI for Women with Ischemic Heart Disease

项目摘要 慢性缺血性心脏病（IHD）是一个价值104亿美元的问题，占死亡人数的45.1% 归因于心血管疾病。与男性相比，女性有不同的IHD谱。电流 诊断工具遵循一种通用的模式，旨在检测男性型IHD。等问题 由于乳腺组织、肥胖症和肺病使得超声或核医学等工具变得容易获得， SPECT成像对女性的限制更大。无阻塞性冠状动脉疾病的缺血更常见于 女性与男性相比;有症状的女性面临的主要心脏事件发生率高于无症状女性 妇女因此，准确的非侵入性工具，能够表征整个频谱的IHD和 其相关缺血负荷对于具有缺血症状的妇女的临床管理是至关重要的。侵入性 干预措施没有风险，缺乏治疗会导致残疾。出现心肌缺血 当新陈代谢需求和血液供应不平衡时。尽管组织血液供应 受心肌血流量（MBF）和心肌血容量（MBV）的影响，电流负荷灌注 策略集中于测量MBF的缺陷，其单独可能不能反映心肌缺血的所有方面。 为了更好地反映缺血负荷，我们提出了一个基于MBV的，全心脏，无钆，非 肾毒性、ferumoxytol对比增强、心脏磁共振成像（MRI）负荷试验 检测诱导性缺血的方法。我们建立在我们的经验，ferumoxytol增强磁共振成像， 通过在缺血的临床前模型中测试我们的策略来增加严谨性;我们有效地将我们的方法转化为 通过在患有IHD的女性中验证该技术，其中一些人需要ferumoxytol进行治疗， 目的由于全世界有20亿人缺铁， 在压力测试的背景下，治疗剂代表了一种定制压力心脏MRI的方法， 经常缺铁的女性。如果我们的项目成功完成， 免费的，ferumoxytol增强的MRI应力测试方法，可以可靠地区分正常与 为心肌负荷试验的发展奠定了基础 能够询问心外膜和微血管IHD的方法。

PROJECT ABSTRACT Chronic ischemic heart disease (IHD) is a $10.4-billion-dollar problem that is responsible for 45.1% of deaths attributable to cardiovascular disease. Compared to men, women have a different spectrum of IHD. Current diagnostic tools follow a one-size-fits-all model and are designed to detect a male pattern of IHD. Issues such as breast tissue, obesity, and lung disease render easily accessible tools such as ultrasound or nuclear SPECT imaging more limiting for women. Ischemia with no obstructive coronary disease is more common in women compared to men; symptomatic women face higher rates of major cardiac events than asymptomatic women. Therefore, accurate non-invasive tools that enable characterization of the entire spectrum of IHD and its correlative ischemic burden are crucial for clinical management of women with ischemic symptoms. Invasive interventions are without risks and lack of therapeutics contributes to disability. Myocardial ischemia occurs when there is an imbalance between metabolic demand and blood supply. Although tissue blood supply is affected by both myocardial blood flow (MBF) and myocardial blood volume (MBV), current stress perfusion strategies focus on measuring deficits in MBF, which alone may not reflect all aspects of myocardial ischemia. To better reflect the ischemic burden, we propose an MBV-based, whole-heart, gadolinium-free, non- nephrotoxic, ferumoxytol contrast-enhanced, cardiac magnetic resonance imaging (MRI) stress testing approach that will detect inducible ischemia. We build upon our experience in ferumoxytol-enhanced MRI and add rigor by testing our strategy in pre-clinical models of ischemia; we efficiently translate our approach to the clinic by validating the technique in women with IHD, some of whom require ferumoxytol for therapeutic purposes. Because 2 billion people worldwide have iron deficiency, the dual use of ferumoxytol as a diagnostic and therapeutic agent in the context of stress testing represents one approach to tailoring stress cardiac MRI for women who are frequently iron deficient. Successful completion of our project would result in a gadolinium- free, ferumoxytol-enhanced MRI stress testing approach that can reliably differentiate between normal vs ischemic myocardial tissue and would establish a foundation for development of myocardial stress testing approaches that enable interrogation of both epicardial and microvascular IHD.